Study Examines Overlap Between Two Common Neonatal Brain Injuries

Brain injuries are a leading cause of death and long-term disability in infants. Among the most common is neonatal hypoxic-ischemic encephalopathy (HIE), which affects 1 to 3 in 1,000 live births per year and accounts for 22% of infant deaths worldwide. Only slightly less common is perinatal arterial ischemic stroke (PAIS).

Both conditions can impact the central nervous system, leading to brain injury and seizures after birth and causing neurological and developmental issues years into a child’s life.

While HIE and PAIS may look similar on paper, researchers behind a recent study published in the journal, Pediatric Research point out that their underlying mechanisms are quite different. HIE is caused by a global reduction of blood flow and oxygen in the brain, while PAIS is caused by a clot that travels into a major arterial vessel of the brain.

The current standard of care for HIE is a therapeutic brain-cooling process aimed at slowing the cellular and molecular damage and inflammation triggered by lack of oxygen.

Using data from a large, multi-center clinical trial examining treatment advancements for HIE, researchers across several U.S. pediatric hospitals including Jessica Wisnowski, PhD, set out to explore how frequently PAIS occurs in infants diagnosed with HIE. They also sought to correlate the presence of PAIS with clinical characteristics like risk of seizure, rate of encephalopathy after brain rewarming and neurodevelopmental outcomes at 2 years of age.

Study setup and results

Study data included 473 infants diagnosed with moderate or severe HIE within 6 hours of delivery, who were enrolled in the HEAL Trial and received brain MRIs.

Researchers found that: 

• 4% of infants with moderate to severe HIE showed MRI evidence of PAIS. 
• 3/4 of infants with PAIS also had an HIE-pattern brain injury and experienced more severe complications than those without PAIS. 
• Seizures were more common in infants with PAIS.
• Infants with PAIS were more likely to have persistent moderate or severe encephalopathy 5 days into treatment than infants without PAIS. 
• Despite the large number of infants with HIE, only 21 had PAIS, limiting researchers’ ability to detect statistically significant differences in 2-year outcomes.

More questions

While researchers made progress in understanding the rate at which both PAIS and HIE occur together, more research is needed to understand the exact timing and pathogenesis leading to these two different neonatal brain injuries.

Potential explanations include:

• HIE and PAIS share similar risk factors like chorioamnionitis and placental disease. 
• HIE may necessitate treatment with ECMO, which in itself is a risk factor for stroke, and which is more common in infants with PAIS. 
• The occurrence of PAIS during labor and delivery may lead to a more difficult and prolonged delivery, which may increase the risk of HIE. 

Next steps

The results demonstrate the value of large-scale studies to help improve interventions for neonatal brain injury. 

“This study emphasizes the importance of brain MRI in identifying all causes of brain injury in infants undergoing therapeutic hypothermia for HIE,” says Dr. Wisnowski. “We hope that this research helps guide diagnosis and treatment advances for these leading causes of infant death and long-term disability.”